Hereditary spherocytosis of man. Altered binding of cytoskeletal components to the erythrocyte membrane

Citations Over TimeTop 10% of 1982 papers

Abstract

Human erythrocytes possess a lattice work of extrinsic proteins on the inner face of the membrane (;cytoskeleton') that maintains the shape and deformability of the cell. The major proteins of the cytoskeleton are spectrin and actin, which are attached to the membrane by protein bands 2.1 (;ankyrin') and 4.1. The interactions of spectrin/actin with erythrocyte membranes from normal subjects and from patients with hereditary spherocytosis (HS) have been studied by using an air-driven ultracentrifuge, which can rapidly separate membranes from soluble proteins (150000g for 30s). The total amount of spectrin/actin in HS and normal ghosts is similar. However, the rate of dissociation of spectrin and actin from HS erythrocyte membranes at low ionic strength is significantly lower than that observed for normal membranes. Spectrin and actin isolated from either HS or normal membranes re-associated in a similar manner to spectrin/actin-depleted vesicles prepared from normal cells. Scatchard analysis showed an average binding capacity of 278mug/mg of membrane protein. However, spectrin/actin-depleted vesicles prepared from HS cells bound significantly less spectrin/actin prepared from either the normal or abnormal cells (average binding capacity 158mug/mg of membrane protein). The defect was defined further by studying the cytoskeleton obtained by Triton X-100 extraction of membranes. Under conditions of low ionic strength cytoskeletons prepared from HS membranes dissociated more slowly than those prepared from normal membranes, and only 80% of the protein from HS cytoskeletons could be solubilized after 180min compared with 100% for normal cytoskeletons. The difference between HS and normal membranes, which persists in isolated cytoskeletons, suggests that alterations in either the primary structure or the degree of phosphorylation of protein bands 2.1 or 4.1 may be central to the molecular basis of hereditary spherocytosis.

Related Papers

• → The membrane attachment protein for spectrin is associated with band 3 in human erythrocyte membranes(1979)434 cited
• → Control of Erythrocyte Membrane-Skeletal Cohesion by the Spectrin-Membrane Linkage(2010)42 cited
• → Hereditary elliptocytosis, spherocytosis and related disorders: Consequences of a deficiency or a mutation of membrane skeletal proteins(1987)90 cited
• → Partial Ankyrin and Spectrin Deficiency in Severe, Atypical Hereditary Spherocytosis(1988)81 cited
• → Modulation of lateral mobility of band 3 in the red cell membrane by oxidative cross-linking of spectrin(1982)50 cited